DESCRIPTION: The functioning of the nervous system depends on the correct specification and "wiring up" of many different neurons in the nervous system. Goulding is interested in elucidating the molecular mechanisms that control the generation of specific neuronal cell types in the developing spinal cord. A large body of evidence suggests that gene regulation by transcription factors plays an important role in patterning the spinal cord. However, very little is known about the mechanisms that control the generation of specific cell types within the spinal cord. The homeodomain transcription factors, En1 and Ev1, are expressed in two populations of differentiating interneurons in the spinal cord. The expression patterns of both genes during development strongly suggest both proteins may function as determinants of neuronal cell type. As a first step toward analyzing the function of these transcription factors, Goulding and colleagues generated taulacZ knock-in mice in order to mark and morphologically characterize the cells that express En1 and Evx1. Goulding and colleagues will use these mice to investigate the fate of these two neuronal populations in mice that lack En1 and Evx1 function. Furthermore, the generation of these knock-in mice will provide valuable tools for further investigating the mechanisms that control cell fate specification and axonal guidance by neurons in the spinal cord. Goulding also plans to examine the regulation of En1 and Evx1 expression by genes that are expressed in the precursors of these cells. The longterm aim of these studies is to molecularly define how these two populations of interneurons are generated during embryonic development.